Energy facilitated composition delivery

ABSTRACT

A device for delivering a composition to a hollow body region is disclosed. In one aspect, the device comprises a first longitudinal member and a second longitudinal member. Both of the longitudinal members may comprise conductive electrodes. The longitudinal members are further configured to be connected to an energy source such that the conductive electrodes are configured to generate an energy field. At least one of the longitudinal members further comprises a delivery element configured to deliver at least one composition to the body region, such that the composition is delivered in a direction that is influenced by the generated energy field. In one aspect, the body region is a vessel comprising an occlusion.

This application is a divisional application of U.S. application Ser.No. 13/560,841 filed Jul. 27, 2012, titled “Energy FacilitatedComposition Delivery”, which is a continuation-in-part application ofPCT/US2011/031018 filed Apr. 1, 2011, titled “Recanalizing OccludedVessels Using Radiofrequency Energy”, which claims priority from U.S.application Ser. No. 12/753,844, filed Apr. 2, 2010, titled“Recanalizing Occluded Vessels Using Radiofrequency Energy”. Thisapplication is also a continuation-in-part application of U.S.application Ser. No. 12/753,844, filed Apr. 2, 2010, titled“Recanalizing Occluded Vessels Using Radiofrequency Energy”, which is acontinuation-in-part of U.S. application Ser. No. 12/680,500, a nationalstage application under 35 U.S.C. § 371, filed Mar. 26, 2010, titled“Recanalizing Occluded Vessels Using Radiofrequency Energy”, whichclaims priority from PCT Application No. PCT/US2008/077403, filed Sep.23, 2008, which claims the priority benefit of U.S. ProvisionalApplication No. 60/975,473, filed Sep. 27, 2007. U.S. application Ser.No. 12/753,844 also claims priority to U.S. Provisional Application Ser.No. 61/298,547, filed on Jan. 26, 2010, titled “Recanalizing OccludedVessels Using Radiofrequency Energy”. The disclosures of the aboverelated applications are incorporated herein by reference.

FIELD OF THE INVENTION

Present embodiments relate generally to delivering a composition to atreatment region in the body under the influence of an energy field.Specifically, present embodiments relate to delivering a composition toan occluded vessel to aid or facilitate the crossing of severe or totalchronic occlusions of lumens in the body.

DESCRIPTION OF THE RELATED ART

Chronic total occlusion (CTO) is the complete blockage of a vessel andmay have serious consequences if not treated in a timely fashion. Theblockage could be due to atheromatous plaque or old thrombus. One of thecommon procedures for treating CTOs of the coronary arteries ispercutaneous transluminal coronary angioplasty (PTCA). During a PTCAprocedure, a small incision is typically made in the groin. A guidingcatheter over a guidewire is introduced into the femoral artery andadvanced to the occlusion. At times, with gentle maneuvering, theguidewire is able to cross the occlusion. A balloon-tipped angioplastycatheter is then advanced over the guidewire to the occlusion. Theballoon is inflated, separating or fracturing the atheroma. Often times,a stent is subsequently or simultaneously deployed. Some of the commonsteps involved in the PTCA procedure for CTOs are the simultaneousinjection of a contrast agent in the contra-lateral vessel, securingbackup force or stabilization for a guidewire (which could invokeadditional personnel to handle the catheter), puncturing the plaque,drilling or rotating the guidewire to push it through the dense plaque,etc. Because of the stiff resistance sometimes offered by dense plaque,one could be forced to use stiff wires. Occasionally, the wires couldpuncture the vessel wall calling for remedial measures.

The most common percutaneous coronary intervention (PCI) failure modefor CTOs is inability to successfully pass a guidewire across the lesioninto the true lumen of the distal vessel. To date, there is no consensuson how best to treat CTO after attempts with conventional guidewireshave failed. Different strategies for CTOs have been developed includingthe side branch technique, the parallel wire technique, and the IVUSguided technique. Mechanical and energy based devices have also beenproposed for passing guidewires through hard calcified occlusions, suchas mechanical cutting or oscillation and laser or ultrasound orradiofrequency (RF) energy ablation. Each of these devices works bystrictly utilizing an antegrade approach and locally applying energy(typically in the form of heat) at the tip of the guidewire or catheterdevice in order to create a channel and hopefully enter the distal truelumen.

RF energy is widely used to coagulate, cut or ablate tissue. In bothmodalities, monopolar and bipolar, conductive electrodes contact thetissue to be treated. In the monopolar mode, the active electrode isplaced in contact with the tissue to be treated and a return electrodewith a large surface area is located on the patient at a distance fromthe active electrode. In the bipolar mode, the active and returnelectrodes are in close proximity to each other bracketing the tissue tobe treated. Sometimes an array of electrodes is used to provide bettercontrol over the depth of penetration of the RF field and hence controlover the temperatures to which the tissue is heated. There are manydisadvantages with each mode. For example, in the monopolar arrangement,because of the large physical separation between the electrodes thereare frequent reports of local burning at the electrode sites. This wouldclearly be undesirable where one of the electrodes will be inside ablood vessel. The other serious issue is the likelihood of forming bloodclots. The tissue that is in contact with the electrodes can becoagulated or ablated. In the case of the electrodes being presentinside a blood vessel, the formation of dangerous blood clots wouldobviously be undesirable.

In an attempt to overcome the issues described above, various device andelectrode configurations are described in the following patents. U.S.Pat. Nos. 5,366,443 and 5,419,767 describe the use of RF electrodes on acatheter to cross a lesion. These patents describe a bipolar electrodeassembly at the distal tip of a catheter that is in contact with theocclusion, and patentees state that application of RF energy ablates theocclusion and renders the occlusion susceptible for the guidewire topenetrate. This method has the drawback that careful tracking of theocclusion and the ablation process is necessary to avoid trauma to thevessel walls or healthy tissue, since the possibility ofshort-circuiting of current through healthy tissue instead of theocclusion is high. U.S. Pat. No. 5,419,767 overcomes this limitation toa certain extent through the use of a multiple electrode array. However,this device requires a channel to be pre-created through the occlusionso that the device can be passed through a guidewire traversing thischannel, which is not always easy.

U.S. Pat. No. 5,514,128 to Hillsman et al. describes a laser catheterdevice that enables ablation of an occlusion in the vasculature. Thissystem has similar drawbacks to the ones described above—need for aguidance system, potential for healthy tissue to be ablated, complexity(and hence cost) of the device, etc.

One major problem with the existing devices is the potential for theablation energy to damage the walls of the vasculature, in the absenceof a mechanism to track the orientation and position of the energydelivery member. Several devices exist in the prior art that address theissue of tracking and steering of the energy delivery element. U.S. Pat.No. 6,911,026 to Hall et al. describes a magnetic steering and guidancesystem to direct an ablation device that delivers RF energy at the tipin a unipolar configuration where the return electrode is placedexternally in contact with the body or in a bipolar configuration wherethe return electrode is a ring surrounding the central wire electrode.

U.S. Pat. No. 6,416,523 to Lafontaine discusses a mechanical cuttingdevice where the guidance is provided by measuring impedance of thetissue in contact. The guidance system senses the difference inimpedance between the stenotic tissue and the vessel wall and directsthe cutting element to the occlusion.

However, none of these alternate strategies have provided satisfactoryresults for the most challenging of the CTOs. In case of hard calcifiedocclusions, the revascularization procedure can be tedious and timeconsuming. Therefore, there is a need for improved methods of ablatingor disrupting the occlusive material that are safe, efficacious andfast. It would be beneficial to have alternate techniques and devicesthat would recanalize a CTO without the shortcomings of the currenttechniques.

SUMMARY OF THE INVENTION

Various methods, devices, and systems configured to deliver acomposition to a treatment region are disclosed. In one aspect, presentembodiments are configured to deliver one or more compositions to anoccluded vessel to aid in the treatment and recanalization of anocclusion.

In one aspect, a device for delivering a composition to a hollow bodyregion comprising a first longitudinal member and a second longitudinalmember. Both of the longitudinal members may comprise conductiveelectrodes. The longitudinal members are further configured to beconnected to an energy source such that the conductive electrodes areconfigured to generate an energy field. At least one of the longitudinalmembers further comprises a delivery element configured to deliver atleast one composition to the body region, such that the composition isdelivered in a direction that is influenced by the generated energyfield. In one aspect, the body region is a vessel comprising anocclusion.

In another aspect, the first longitudinal member is configured toapproach the body region in an antegrade fashion and the secondlongitudinal member is configured to approach the body region in aretrograde fashion.

In another aspect, the energy source is a radiofrequency energy sourceand one of the conductive electrodes is an active electrode and anotheris a passive electrode. In one aspect, the composition is delivered in adirection from the active electrode to the passive electrode. In yetanother aspect, the composition is delivered in a bi-directional fashionbetween the conductive electrodes. In still yet another aspect, thecomposition is a conductive fluid and the conductive fluid forms anenergy path between the conductive electrodes, wherein the energy pathis configured to facilitate energy transmission between the conductiveelectrodes. In another aspect, the conductive fluid energized by theenergy field is configured to ablate a portion of the body region.

In one aspect, the device comprises at least one composition reservoirconfigured to hold the composition, wherein the composition reservoir isconnected to the delivery element through one or more lumens disposedwithin at least one of the longitudinal members.

In another aspect, the longitudinal members may be configured asguidewires, catheters, micro-catheters, or dilating catheters

In another aspect, the energy source is configured to generate anelectric field, a magnetic field, or ultrasonic field.

In one aspect, the composition is isotonic saline, in another aspect,the composition is collagenase, in yet another aspect, the compositionis a biocompatible gas.

Present embodiments also disclose a device for recanalizing an occludedvessel. In one aspect, the device comprises a first longitudinal membercapable of being advanced in an antegrade fashion through a proximal endof the occlusion, a second longitudinal member capable of being advancedin an retrograde fashion through a distal end of the occlusion, whereinat least one of the longitudinal members further comprises a deliveryelement configured to deliver at least one composition to the occludedvessel, such that the one or more composition is delivered to treat theoccluded vessel.

Other aspects of the invention include methods corresponding to thedevices and systems described above.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention has other advantages and features which will be morereadily apparent from the following detailed description of theinvention and the appended claims, when taken in conjunction with theaccompanying drawings, in which:

FIG. 1 is a schematic showing an RF generator connected to thelongitudinal members.

FIG. 2 shows one embodiment of the longitudinal members.

FIGS. 3A-3B show various embodiments of longitudinal members comprisinginsulators.

FIG. 4 show one embodiment of the longitudinal member comprising acomposition delivery element.

FIGS. 5A-5C show various views of one embodiment of a delivery catheter.

FIGS. 6A-6B show various views of another embodiment of a deliverycatheter with coaxial shafts.

FIGS. 7-8 show steps of delivering a composition to an occluded vesselto aid in vascular recanalization.

FIG. 9A-9C shows an exemplary embodiment of conductive electrodesconfigured to expand outwardly.

FIG. 10 shows an exemplary embodiment of a longitudinal membercomprising an embolic protection mechanism.

DETAILED DESCRIPTION

Although the detailed description contains many specifics, these shouldnot be construed as limiting the scope of the disclosure but merely asillustrating different examples and aspects of the disclosure. It shouldbe appreciated that the scope of the disclosure includes otherembodiments not discussed herein. Various other modifications, changesand variations which will be apparent to those skilled in the art may bemade in the arrangement, operation and details of the method andapparatus disclosed herein without departing from the spirit and scopeof the disclosure as described here.

The present embodiments relate to systems, devices, and methods ofdelivering one or more compositions to a hollow body treatment region.Specifically, one embodiment of the present disclosure relates to usingmultiple energy delivery longitudinal members to create an energy fieldwhereby a composition is delivered to the treatment region at a rate orin a direction influenced by the generated energy field.

As referred to herein, a hollow body region includes any vessel orartery in which blood flows through a hollow tubular cavity as well asany duct or lumen within the body. In one embodiment, the hollow bodyregion is a body vessel comprising an occlusion. An occluded body vesselmay obstruct the blood flow and could have fatal consequences.Typically, the occlusion comprises a distal cap, a proximal cap, and anocclusion body therebetween. The occlusion could be atheromatous plaque,old thrombus, or similar other deposits.

As disclosed in U.S. Pat. No. 7,918,859 by the same inventors, which isincorporated herein in its entirety, in the controlled antegrade andretrograde tracking (CART) technique the retrograde approach takesadvantage of an intercoronary channel. Such a channel may be anepicardial channel, an inter-atrial channel, an intra-septal channel(also referred to as septal collateral), or a bypass graft. The basicconcept of the CART technique is to create a channel through anocclusion, preferably with limited dissections, by approaching theocclusion both antegradely and retrogradely.

While the combined antegrade and retrograde approach has been effectivein crossing difficult to cross lesions, it has been observed that usingenergy, for example radiofrequency (RF) energy, to ablate or alter thetissue in a controlled fashion is beneficial in crossing hard to crosslesions. Such controlled energy deployment is achieved using a bipolararrangement of the electrodes, where one electrode is located on theantegrade element and the other electrode that constitutes the bipolararrangement is located on the retrograde element. These electrodes canalso be referred to as the return and active electrodes. They are alsoreferred to as the anode and cathode, respectively. The electrodes couldalso be arranged in an array (multiple electrodes), where the electrodearrangement provides better control over the depth of penetration of theRF field and thereby provides the ability to control the tissuetemperature.

By taking advantage of an antegrade and retrograde approach to establisha bipolar electrode arrangement across the occlusion, it is possible toleverage the generated energy field to recanalize difficult to crossocclusions. This approach minimizes the potential of the vessel wallbecoming perforated or injured, as may otherwise occur in a conventionalbipolar energy treatment approach, where both electrodes are on the sameside of the occlusion. Because the electrodes are distributed onopposite sides of the occlusion, the tissue that is ablated by theenergy treatment (i.e., the occlusion) is well contained between theelectrodes. This also allows the user to localize the treatment to theocclusion.

To facilitate the bipolar energy delivery treatment, present embodimentscontemplate delivering one or more compositions to a treatment regionsuch as an occluded vessel. An energy field generated by the bipolarelectrode arrangement of the longitudinal members is configured toaffect, propel, or influence the rate and/or the direction that thecompositions migrate within or through the treatment region. Thecomposition may be conductive fluid, which may facilitate energydelivery between the longitudinal members and ablation by creating anenergy sink and/or a conductive fluid path between the longitudinalmembers. Additionally or alternatively, the composition may beconfigured as a therapeutic agent, such that the therapeutic agent maybe delivered to the treatment region under the influence of andfacilitated by the generated energy field. Additionally, the compositionmay also be configured as a contrast agent or visualization agent.

FIG. 1 shows a system for delivering a composition to a treatmentregion, such as an occluded vessel facilitated by an energy modality.The system comprises longitudinal members 100 a and 100 b for deliveringenergy, such as RF energy, to the treatment region. As indicated in FIG.1, the first longitudinal member 100 a serves as an antegrade member,such that the first longitudinal member 100 a is configured to approachthe treatment region in an antegrade fashion, and the secondlongitudinal member 100 b serves as a retrograde member, such that thesecond longitudinal member 100 b is configured to approach the treatmentregion in an retrograde fashion.

An energy source, such as a source that provides an electric field, amagnetic field, high energy waves like laser or ultrasonic energy, of acombination thereof is configured to be connected to the longitudinalmembers 100 a and 100 b. In one embodiment, the energy source is an RFgenerator 10 (also referred to as a controller) which serves as thesource of RF energy. Optionally, the RF generator may be a hand-heldbattery-operated device. Longitudinal members 100 a and 100 b may beguidewires, catheters, micro-catheters, or dilating catheters. In apreferred embodiment, longitudinal members 100 a and 100 b areguidewires. Additionally, longitudinal members 100 a and 100 b areconfigured to have sufficient torsional rigidity and longitudinalflexibility to advance through tortuous anatomy or dense materials suchas an occlusion, and to align their electrodes in a direction away fromtissues such as the vessel wall, towards the other longitudinal member,or any combination thereof.

As shown in FIG. 2, the longitudinal members 100 a and 100 b haveconductive electrodes 105 a and 105 b, respectively, at their distalends. In one embodiment, where the treatment region is a occludedvessel, the electrodes 105 a and 105 b are located on one side of theirrespective longitudinal members 100 a and 100 b, thereby providing theoperating physician with the freedom to allow the electrode-free side ofthe longitudinal members to touch the vessel wall (if needed) whilestill directing the RF energy away from the vessel wall. Additionally,this allows the configuration to direct the RF energy away from thevessel wall, thereby minimizing potential RF injury to the vessel wall.In one embodiment, one or more of the longitudinal members comprises aplurality of electrodes arranged in an array.

Conductive wires (not shown) connect the electrodes 105 a and 105 b ofthe longitudinal members, respectively, to connector 30 to deliver RFenergy from the RF generator 10 to the electrodes 105 a and 105 b. Theexterior of the longitudinal members are covered by non-conductivelayers 115 a and 115 b, respectively, which sandwich the conductivewires between the longitudinal members and the non-conductive layers. Inone embodiment, the nonconductive layers 115 a and 115 b comprise asheath or a coating. Examples of materials may include Teflon, ceramic,polyimide, parylene, or other suitable materials. Examples of methodswhich could be employed for coating may include spraying, dipping, vapordeposition, or plasma deposition. In another embodiment, the conductivewires are insulated by using a heat resistant material on the guidewireto protect the device and surrounding tissue from excessive heat.

FIG. 3A shows a cross-sectional view of a longitudinal member comprisingan electrode and an insulator, in accordance with an embodiment of thepresent invention. A longitudinal member 200 comprises an electrode 210as its distal tip. The electrode 210 is electrically coupled to thelongitudinal member's corewire via an electrically conductive ribbon 220or other such electrically conductive connector. An insulator 230 isdisposed at a distal portion of the guidewire 200 to deflect some of theheat that is generated when the electrode 210 is energized withradiofrequency energy, thereby protecting the rest of the device fromsuch heat. The insulator 230 may wrap around the distal portion of thelongitudinal member 200, as shown in FIG. 3A, or it may be configured asa plurality of discrete pieces disposed at the distal portion of theguidewire 200. The insulator may or may not directly contact electrodes.

In another embodiment, the insulator may be configured to protrudeforward so that the electrode is recessed. An example of this is shownin FIG. 3B, showing a protruding insulator 240 configured to extendbeyond the electrode 210, thereby recessing the electrode 210. Thislimits the exposure of the electrode 210 to surrounding tissue, whileleaving the electrode sufficiently exposed to create the bipolararrangement.

To provide RF energy from the RF generator 10 as seen in FIG. 1, to thelongitudinal members 100 a and 100 b, a pigtail 20 connects at itsproximal end to the RF generator 10 and terminates at its distal end ina connector 30. Connector 30 is a standard connector that couples theinput and output signals of the RF generator 10 to the longitudinalmembers 100 a and 100 b.

One embodiment of the connector would be a locking tool or torque devicewhich can be placed over the guidewire. In such a configuration, thelocking tool or torque device is configured to make electrical contactwith a portion of the longitudinal member (such as corewire) thatconducts radiofrequency energy to, or from, the one or more electrodesdisposed on the longitudinal member. In such a configuration, thelocking tool or torque device would also be configured to connect to aradiofrequency generator, thereby electrically connecting the generatorto the longitudinal member and electrodes. Means of locking theconnector to the guidewire may include compressible prongs, screws,sliding rings, or other mechanisms commonly utilized in torque devices.

In one embodiment, and as further shown in FIG. 2, the longitudinalmembers 100 a and 100 b comprise temperature measuring elements 110 aand 110 b at the distal tip of the antegrade and retrograde longitudinalmembers, respectively. In one embodiment, the temperature measuringelements 110 a and 110 b comprise thermocouples or thermistors that areconnected to the connector 30. In another embodiment, pressure measuringelements are placed on the distal ends of the guidewires to detect achange in pressure upon activation of the RF energy.

RF generator 10 is configured to allow the user to set a maximumtemperature, a treatment time period, a level of RF power, or acombination of these control parameters. The treatment time periodindicates the period of time over which the RF energy will flow betweenthe electrodes. The maximum temperature setting serves as a thresholdtemperature for the tissue that is in contact with the electrodes, andthe RF generator 10 can be set to reduce or shut off power to one orboth electrodes when one or more of the temperature measuring elements110 a and 110 b indicate a tissue temperature at or near the threshold.

In one embodiment, the generator 10 is capable of measuring theimpedance of the tissue between the two electrodes 105 a and 105 b.Based on the type of the occlusion (i.e., the nature of the calcifiedmaterial), the user can choose the appropriate combination oftemperature, treatment time, and the amount of RF energy to be providedto the tissue to achieve a safe and effective treatment. Alternatively,the treatment may proceed with the user manually controlling theparameters during the recanalization procedure, with the user treatingthe occlusion until recanalization is achieved.

One or both of the longitudinal members further comprise at least onedelivery element configured to deliver one or more compositions to thetreatment region. As seen in FIG. 4, in one embodiment, the deliveryelement is disposed within the interior of the longitudinal member. Inone embodiment, the delivery element 310 comprises a distal deliveryport 311 disposed substantially near the distal end of the longitudinalmember 300, a proximal supply port (not shown), and a delivery shaft 312disposed in-between. The supply port is configured to be connected withone or more composition reservoirs and/or other delivery mechanisms. Thedelivery port 311 is configured to deliver at least one composition tothe treatment region, wherein the composition may be transmitted to thedelivery port 311 from the composition reservoirs through the deliveryshaft 312.

Additionally or alternatively, the delivery element 310 may comprise aninjection port (not shown) that traverses the coating of thelongitudinal member 300 to connect one or more composition reservoirswith the delivery shaft 311 of the delivery element 300. In suchembodiment, the delivery shaft 311 may be coated with materials, such ashydrophobic materials that are configured to prevent the compositionfrom exiting the delivery shaft 311.

Alternatively, the delivery element may be independent of thelongitudinal member. In one example, present embodiments contemplate amulti-lumen delivery catheter configured to accommodate a longitudinalmember and/or a delivery element, as well as acting as the deliveryelement. As seen in FIG. 5A, the multi-lumen catheter comprisingcatheter shafts 410, 420, and 430. The inner shaft 430 as defined by aguidewire lumen 450 and a thin wall 451 is configured as a guidewireshaft to accommodate the longitudinal member. The delivery elementcomprises a delivery port 440 and a delivery shaft that is defined bythe wall 451 of the inner shaft 430 and wall 445 of shaft 420. Innershaft 430 extends the entire length of catheter 400. To facilitateidentification of the location of the delivery catheter 400, inner shaft430 may contain a radiopaque marker 431 adjacent to the distal tip ofinner shaft 430.

FIG. 5B shows the cross-section of shaft 420. FIG. 5C shows the crosssection at the proximal end of the catheter 410. Each of shafts 410,420, and 430 can be made of any number of polymers including but notlimited to nylon, PEBAX, polyurethane, polyethylene and polyimide. Acomposition that is injected at the proximal end of the catheter exitsthe delivery port 440. FIG. 5C also shows the guidewire lumen 450 and aguidewire channel with an optional braided lining 460 and an optionalPTFE lining 455. A typical ID for the guidewire lumen 250 would be about0.39 mm but can range from 0.15-1.0 mm. A typical OD for the cathetershaft 430 would be 0.83 mm but can range from 0.5-2.0 mm.

Often, the passageways to the treatment region may be tortuous andimpede the progress of the delivery catheter. Therefore, the multi-lumendelivery catheter described above may be modified for improvedmaneuverability. In an alternative embodiment of the delivery catheter,two shafts are detached from each other but are contained coaxiallywithin one another. In such an embodiment, the inner shaft is theguidewire shaft, and the outer shaft is the delivery shaft. Acomposition is injected proximally into a supply port, travels throughthe space between the two coaxial shafts, and flows distally out of adelivery port. This coaxial arrangement allows the two lumens to retaintheir functionality, while decreasing the rigidity that would be createdby an attached multi-lumen configuration. Furthermore, having thecomposition and the longitudinal member in separate lumens furtherenhances guidewire maneuverability. The added maneuverability andflexibility decreases the likelihood of the catheter kinking as itnavigates tortuous pathways, thereby allowing for improved access to thetreatment region as well as improved delivery of the composition.

FIG. 6A shows an exemplary embodiment of such a delivery catheter havinga coaxial multi-lumen configuration. The delivery catheter comprises adelivery shaft 520, and an inner guidewire shaft 530. The inner diameterof delivery shaft 520 is larger than the outer diameter of guidewireshaft 530, such that guidewire shaft 530 resides coaxially withindelivery shaft 520, but is not attached to injection shaft 520. Theproximal end of guidewire shaft 530 is coupled to a hub 505, whereas thedistal end of the guidewire shaft 530 is free-floating within deliveryshaft 520. Delivery shaft 520 comprises a wall 541 and a delivery shaftlumen 540. Guidewire shaft 530 comprises a wall 551 and a guidewirelumen 550. A composition, when injected proximally into supply port 510,travels through the space between the two shaft walls 551 and 541, andflows distally out of the delivery catheter 500. Optionally, the distaltip of the guidewire shaft 530 or the delivery shaft 520 may comprise aradiopaque marker 560, as shown.

In the embodiment shown in FIG. 6A, the length of guidewire shaft 530 isshorter than the length of delivery shaft 520. Alternatively, the lengthof guidewire shaft 530 may be longer than the length of delivery shaft520, or the same length as the delivery shaft 520.

FIG. 6B shows a cross-section of the delivery device of FIG. 6A, showingdelivery and guidewire shaft walls 541 and 551, and delivery andguidewire lumens 540 and 550. Each of the shaft walls 541 and 551 may bemade of one or more polymers, including but not limited to nylon, PEBAX,polyurethane, polyethylene and polyimide. Optionally, the inside of theguidewire shaft wall 551 is lined with a material having a lowcoefficient of friction, for example PTFE or high-density poly-ethylene,to facilitate movement of the longitudinal member within the guidewirelumen 550.

Optionally, the guidewire shaft 530 and/or the delivery shaft 520 maycomprise a plurality of segments made of materials with differingdurometers, thereby allowing finer control of the flexibility along thelength of the shaft. For example, in one embodiment, the proximal end ofthe guidewire shaft 530 may comprise a braid, increasing the rigidityand allowing a user to advance the delivery catheter by providing aforce proximally, whereas the distal end of the guidewire shaft 530 maycomprise a coil, increasing the flexibility and allowing the deliverycatheter to follow tortuous passageways without kinking Optionally, theleading edge of the delivery catheter may comprise a soft tip to promotemaneuverability and prevent damage to the vessel wall.

The composition reservoir may be configured as an intravenous drip bag,a pressurized intravenous drip bag, a locking syringe, drug cartridge,or the like. Optionally, supply port or injection port as describedabove may be pressurized to facilitate a continuous flow of thecomposition from the reservoir.

Optionally, the proximal opening of the delivery element may beconfigured to connect to the composition reservoir via a deliverycontroller, wherein the delivery controller is configured to controlcomposition delivery. In one embodiment, the delivery controller may beconfigured to control the rate of the composition delivery and theamount of composition delivered to the treatment region. Additionally,the delivery controller may be connected to two or more compositionreservoirs which hold different compositions. In such embodiment, thedelivery controller enables the operator to choose which composition todeliver to the treatment region.

In one embodiment, the delivery controller comprises a drive mechanismfor discharging the composition from the composition reservoir. In oneembodiment, the drive mechanism comprises a precision screw that isconfigured to transmit movement to a vertical micro-lever, whichactivates a plunger, stem and piston against the composition reservoir.The drive mechanism further comprises a micromotor configured to drivethe composition to the delivery element. In one embodiment, the rotationof the micromotor is designed to be unidirectional, which preventsbackward movement or the stem, thereby preventing negative pressurebuild-up and undesirable reverse inflow of fluids back into thecomposition reservoir. Additionally and optionally, the deliverycontroller may further comprise one or more microcontrollers comprisingCPU, clock, memory and/or user interface. The microcontroller may beconfigured to control composition delivery from the reservoirs and maybe programmed to store one or more dosing parameters or treatmentschedules.

The conductive electrodes disposed on the longitudinal members areconfigured to generate an energy field, such as an RF energy field,whereby under the influence of the energy field, the compositiondelivered by the delivery element is configured to substantially migrateeither in the direction towards the active electrode or the passiveelectrode and/or facilitate the rate of migration. In one embodiment, itis contemplated that a composition delivered through one or moredelivery elements may facilitate energy delivery across the electrodes.

In one embodiment, the composition is configured as a conductive fluid.A conductive fluid may be any fluid comprising positive or negativecharges, such as isotonic saline. In one embodiment, the conductivefluid may be delivered to the treatment region through the longitudinalmember comprising the passive electrode, the conductive fluid therebyimmerses a portion of the treatment region such that the activeelectrode disposed on the other longitudinal member may generate acurrent density that is sufficiently high to cause sparks crossing overto the fluid immersed portion of the treatment region. In such anembodiment, the fluid may acts as an energy sink, thus receiving theenergy delivered from the active electrode.

In another embodiment, the conductive fluid may migrate through thetreatment region influenced or facilitated by the energy field createdby the electrodes. For example, a negatively charged conductive fluidmay be delivered to the treatment region from one longitudinal memberwhereby the negatively charged conductive fluid is attracted andmigrates towards the positive charge generated by the other longitudinalmember. Alternatively, a positively charged conductive fluid may bedelivered to the treatment region whereby the fluid is attracted andmigrates towards the negative charge generated by the longitudinalmember. Furthermore, the composition may be delivered in abi-directional fashion between the first and longitudinal members. Themigration of the conductive fluid forms a conductive fluid path betweenthe longitudinal members which may facilitate energy delivery betweenthe longitudinal members. In one embodiment, the conductive fluid maypenetrate at least a portion of the occlusion in the vessel bytraversing substantially through pores or channels in the occlusion,thereby creating a conductive fluid path within or through theocclusion.

Furthermore, it is envisioned that the energy as applied from theelectrodes may be sufficient to energize the conductive fluid such thatthe conductive fluid may ablate materials in contact with the fluid. Forexample, the energy as applied from the electrodes may be sufficient toheat the conductive fluid or vaporize the conductive fluid such thatplasma may be formed to cause disintegration or breakdown of theocclusion in contact with the plasma. In one embodiment, a conductivefluid path may be initially created by applying energy through theelectrodes to create an energy field that drives or propels themigration of the fluid. Thereafter, the energy as applied through theelectrodes may be increased such that at least a portion of the fluidalong the conductive fluid path is at least partly vaporized to ablatethe material along the fluid path.

Another embodiment of the present device, methods, and systems isconfigured to deliver a composition configured as a therapeutic agent tothe treatment region by using an energy field to facilitate thecomposition delivery. In one embodiment, the therapeutic agent may beconfigured as a charged compound, such that after the therapeutic agenthas been delivered through the delivery element, the therapeutic agentis configured to migrate under the influence of the energy field asgenerated by the electrodes. Additionally or alternatively, aelectrically neutral therapeutic agent may be modified by adding acharged moiety such that the modified therapeutic agent comprising thecharged moiety may be more susceptible to the influence of the energyfield. Additionally, the therapeutic agent may be submerged of dissolvedin a conductive fluid, whereby the conductive fluid path under theinfluence of the energy field as described above serves as a vehicle tofacilitate the delivery of the therapeutic agent to the treatmentregion.

It is contemplated that the therapeutic agent may be any compositionthat has a therapeutic effect to the treatment region. For example,therapeutic agent may be collagenase, or various other drugs ortherapeutic substances.

In another embodiment the composition delivered to the treatment regionmay be used as a coolant to control the temperature of the treatmentregion during the ablation procedure. Additionally and optionally, thecomposition delivered to the treatment region may be used to weakenand/or break up a portion of the tissue to facilitate furthertreatments. For example, to treat an occluded vessel, the compositionmay be configured as compressed biocompatible gas such as CO₂, and thecompressed gas is delivered into the occlusion before or during theadvancement of the longitudinal member to create, enlarge, or expand aspace in the occlusion to facilitate further penetration of theocclusion by the longitudinal member or composition delivery.Furthermore, it is contemplated that the composition may be a contrastagent configured to aid in visualization of the treatment region. Forexample, delivering a contrast agent at the appropriate location mayreveal the available septals to facilitate identification of anappropriate channel while simultaneously advancing and manipulating thelongitudinal members.

It is further contemplated that multiple compositions may be deliveredin sequence or in tandem to the treatment region. In one embodiment,where the treatment region is an occluded vessel, a first compositionconfigured to weaken and/or break up a portion of the occlusion is firstdelivered to the treatment region. As described above, the firstcomposition may create or expand a space in the occlusion. Thereafter, asecond composition is delivered to the treatment region. The secondcomposition may migrate into the occlusion through the space affected bythe first composition, thus facilitating the delivery of the secondcomposition into the occlusion. In one embodiment, the secondcomposition is configured as a conductive fluid, and the conductivefluid may deposit at least partly within the space affected by the firstcomposition and thereafter acts as an energy sink by receiving theenergy delivered from the active electrode. The conductive fluid mayalso form a conductive fluid path traversing at least partly through thespace affected by the first composition. In another embodiment, thesecond composition may be a therapeutic agent as described above. Thespace affected by the first composition may act as a depository for thetherapeutic agent into the treatment region or it may facilitate thetherapeutic agent delivery through the occlusion as driven by the energyfield as applied by the electrodes.

In another embodiment, the first composition may be a conductive fluidconfigured to facilitate energy ablation as described above. After theablation process has been at least partly carried out, a secondcomposition configured as a therapeutic agent may be delivered to thetreatment region where the therapeutic agent may be deposited ordelivered through the space created by the ablation process.Additionally or alternatively, the therapeutic agent may be appliedinitially, and the conductive fluid may be delivered thereafter. It iscontemplated that multiple therapeutic agents may be delivered to thetreatment region. Furthermore, more than two compositions may be used,for example, the first composition may be delivered to create or expanda space in the occlusion, a second composition may be delivered tofacilitate energy conduction, and a third composition may be deliver asa therapeutic agent to further treat the occlusion.

It is contemplated that multi composition delivery may be achieved byusing the delivery controller and multiple composition reservoirs. Forexample, the sequence of delivering multiple compositions may beprogrammed and stored within the memory of the microcontroller of thedelivery controller, such that the microcontroller may automaticallyselect the type and amount of the composition delivered depending on theprogrammed treatment regime.

One exemplary sequence of treating an occluded vessel using oneembodiment of the composition delivery device is illustrated in FIGS. 7and 8. As shown in diagram A of FIG. 7, the first longitudinal member100 a and second longitudinal member 100 b are advanced to the proximaland distal ends 610 a and 610 b of the occlusion 610, respectively. Thiscan be accomplished using standard angioplasty techniques. As describedin the above referenced U.S. Pat. No. 7,918,859, the first longitudinalmember may be a retrograde longitudinal member, which can be advanced tothe distal end of the occlusion 610 b using collaterals such as theseptals. Additionally and optionally, a composition configured to weakenand/or break up a portion of the occlusion may be delivered to theocclusion through the delivery element prior to and/or contemporaneouswith the advancement of the longitudinal members.

Once the operator has confirmed that the longitudinal members 100 a and100 b are in contact with the occlusion 610 and are not touching thevessel wall 600, a RF energy field is generated through the electrodesdisposed on the longitudinal members. Prior to and/or contemporaneouswith generation of the RF energy field, a composition configured as aconductive fluid may be delivered to the treatment region such that theconductive fluid may act as an energy sink, which may help sustain oramplify the generated RF energy field.

Alternatively, the longitudinal members are advanced as deep into theocclusion as possible to minimize the distance between the electrodesand, consequently, minimize the length of the energy field. Again, acomposition configured to weaken and/or break up a portion of theocclusion may be delivered to the occlusion through the delivery elementprior to and/or contemporaneous with the advancement of the longitudinalmembers. Confirmation that the longitudinal members 100 a and 100 b arein an appropriate position can be generated by impedance measurementsand/or by using any of the standard imaging techniques employed duringinterventional procedures, such as fluoroscopy or intravascularultrasound (IVUS), in which transducers are placed on the distal ends ofthe longitudinal member. When using tissue impedance measurements, thecalcified occlusion 610 generally exhibits significantly higherimpedance than the vessel wall 600. If an impedance measurementindicates a low impedance value, it is likely that one or bothlongitudinal members are in contact with the vessel wall 600, andappropriate repositioning of the longitudinal members may be warranted.

It is further noted, that it may not be required for the longitudinalmembers to penetrate the occlusion to create an energy field. In fact,it may be sufficient for the longitudinal members to be positionedwithin proximity where the RF spark may cross from the active electrodedisposed on one longitudinal member to the return electrode disposed onthe other longitudinal member to achieve the energy field. For example,the second longitudinal member may be positioned within the distal truelumen of the occluded vessel, and the first longitudinal member may bepositioned within the occlusion, RF energy may then be delivered betweenthe active and return electrodes to create an energy field between thetwo longitudinal members.

Upon initiating the RF energy field, a composition configured as aconductive fluid may be delivered into the occlusion such that theconductive fluid forms a fluid path under the influence of the energyfield. For example, the conductive fluid may migrate from a position ator close to the passive electrode towards the active electrode, whiletraversing at least a part of the occlusion. The conductive fluid pathmay facilitate energy transmission between the longitudinal members.Furthermore, the conductive fluid may absorb the RF energy along theconductive fluid path such that the fluid may be sufficiently heated orvaporized to form a plasma to cause disintegration or breakdown of theocclusion in contact with the fluid or plasma. In one embodiment, theocclusion 610 is ablated along the conductive fluid path from the ends610 a and 610 b of the occlusion 610 to the interior of the occlusion610, as shown in FIG. 7 diagram B.

Thereafter, the user then slowly and carefully advances one or bothlongitudinal members 100 a and 100 b until a channel or path is createdin the occlusion 610, as shown in FIG. 7 diagram C. As shown in FIG. 7,the antegrade longitudinal member 100 a may be kept stationary and theretrograde longitudinal member 100 b may be advanced through theocclusion 610. Once a channel has been created, the retrogradelongitudinal member 100 b may be withdrawn and the antegradelongitudinal member 100 a may be advanced through the occlusion 610, asshown in FIG. 7 diagram D, and standard interventional procedures, suchas balloon angioplasty, can be performed. Alternatively, the retrogradelongitudinal member 100 b can be kept stationary during the RF treatmentand composition delivery, where the antegrade longitudinal member 100 acan be advanced through the occlusion 610. This is illustrated in FIG. 8diagrams A-D.

Additionally or alternatively, during various steps of treatment, acomposition configured as a therapeutic agent may be delivered into theocclusion such that the therapeutic agent migrates through the occlusionunder the influence of the energy field.

It is noted that energizing an electrode with RF energy causes theelectrode to generate heat. In general, the amount of such heat isproportional to the amount of radiofrequency energy delivered to theelectrode, and inversely proportional to the surface area of theelectrode. This is because the smaller the surface area of an electrode,the higher the current density passing through that surface area (for agiven total current), which in turn causes the electrode to reachcorrespondingly higher temperatures. In one embodiment, the system isconfigured to deliver sufficient radiofrequency energy to an electrodesuch that radiofrequency sparks are generated.

While it is possible to have the surface areas of the active and returnelectrodes be of similar size, in a preferred embodiment an activeelectrode is configured to have a smaller surface area than a returnelectrode. This allows the active electrode to generate sufficientcurrent or energy density to affect cutting or ablating and spark overto the return electrode, while at the same time allowing the returnelectrode surface area to be sufficiently large so as to maximize itscontact with the occlusion and act as a sink for the energy emitted fromthe active electrode. Additionally, it is contemplated that acomposition configured as a conductive fluid may be delivered throughthe longitudinal member comprising the passive electrode, such that theconductive fluid may act as an additional energy sink for the energyemitted from the active electrode. Another advantage of such anembodiment is that the return electrode will likely not reach as hightemperatures as the active electrode. In addition, the conductive fluidmay also acts as a heat sink or coolant for the passive electrode. Inone embodiment, the ratio of the return electrode surface area to theactive electrode surface area is configured to be in the range of about50:1 to about 1:1, and preferably about 10:1. In one embodiment, thereturn electrode is configured in a pigtail design to increase surfacearea contact with the occlusion.

In another embodiment, a plurality of return electrodes may beconfigured to expand outwardly in order to spread out and increasesurface area contact with the occlusion. Such an embodiment is shown inFIG. 9A, where a plurality of ribs 610 are disposed on a distal end 620of a longitudinal member 600. The ribs 610 are configured to flare out,as shown in FIG. 9B. In a collapsed state, the ribs 610 are kept undertension, for example by using a restraining sleeve (not shown), bytwisting the ribs 610, by exerting a stretching or pulling force on theproximal ends of the ribs 610, etc. The longitudinal member 600, withthe ribs 610 in a collapsed state, is advanced into the occlusion. Uponreleasing the tension or pulling back on the restraining sleeve, theribs 610 flare open.

In another embodiment, the ribs 610 comprise electrode areas 630adjacent to insulator areas 640, as shown in the cross-sectional view ofFIG. 9C. In such an embodiment, when the ribs 610 flare out into abasket-like configuration, the insulator areas 640 are on the outsideand the electrode areas 630 are on the inside of the basket-likeconfiguration. This configuration advantageously aids in directingradiofrequency energy inside the basket-like configuration whilesimultaneously providing protection to the surrounding tissue.Alternatively, it is contemplated that in other embodiments theplacement of the electrode areas 630 and insulator areas 640 may bevaried. In an optional embodiment, a capture device may be configured tocomprise one or more electrode areas for use as return electrodes.Examples of capture devices are disclosed in the co-pending U.S. patentapplication Ser. No. 12/150,111 by the same inventors, which isincorporated herein in its entirety.

Optionally, a centering balloon catheter can be utilized along with thelongitudinal members to center the guidewire within the vessel prior toenergizing the system. In such a configuration, it would be advantageousto have a heat resistant tip on the distal end of the balloon catheter.

Optionally, the catheter comprises a means for removing or withdrawingdebris resulting from the RF ablation. For example, a mechanism could beprovided to capture and retrieve the debris, or a suction device couldbe provided to actively remove the debris near the ablation area.Examples of such embolic protection mechanisms are disclosed in theabove referenced U.S. Pat. No. 7,918,859. FIG. 10 shows an exemplaryembodiment of a longitudinal member 700 comprising an embolic protectionmechanism 710. The embolic protection mechanism 710 comprises a filter,mesh, net, or similar element, for capturing and retrieving ablationdebris. As another example, the embolic protection may comprise aballoon for occluding the vessel and preventing the debris fromcirculating, and for subsequent aspiration of the debris through alongitudinal member. As another example, if a sheath is provided, suchsheath may also be configured to be or to include a debris capture andretrieval mechanism or a suction device. In one embodiment, alongitudinal member may be retracted, and the remaining sheath may beused as a capture and retrieval mechanism or a suction device to removeablation debris. In another embodiment, the longitudinal membercomprises an ablating wire housed in the lumen of a dilating catheter.Upon ablation, the ablating wire may be retracted and the dilatingcatheter may be used to remove the debris. Alternatively, the systemcomprises a separate catheter to provide suction, or otherwise captureand remove the debris from the ablation site.

Optionally, present embodiments may be coupled to an electrocardiogram(EKG) machine to aid in timing energy emissions. For example, the rateof blood flow through the coronary arteries typically varies during thecardiac cycle. During systole when the heart is contracting, flowthrough the arteries is generally lower than during diastole. In oneembodiment, energy emission is timed during diastole, for example usingan algorithm to detect the R-wave of an EKG, and energy emission istimed to occur when flow is highest, thereby maximizing the coolingeffect provided by blood flow and consequently minimizing the heatexposure to the vessel. Additionally, coronary artery dimensions canvary during the cardiac cycle and energy emission can similarly be timedto take advantage of this fact.

Optionally, present embodiments may be configured to perform an imagingfunction, such as intravascular ultrasound or optical coherencetomography (OCT). In one embodiment, this may be accomplished by addinga piezoelectric crystal to a longitudinal member of the device, whereinthe piezoelectric crystal may be energized to transmit or receiveultrasonic waves. In another embodiment, an imaging core may be insertedinto a longitudinal member of the device (e.g., in the case of adilating catheter) and operated to transmit and receive ultrasonicwaves. In another embodiment, an optical fiber may be used forperforming OCT imaging.

Optionally, present embodiments comprise a mechanism for detecting orestimating the distance between the electrodes, and for decreasing theamount of delivered RF energy as the distance between the electrodesdecreases, thereby minimizing potential RF injury to the vessel wall.

Various embodiments of the longitudinal members and electrodes may bemade from any one or more suitable materials as is commonly known in theart. Examples of such suitable materials include stainless steel,Nitinol, Elgiloy, platinum, iridium, tantalum, titanium, cobalt,chromium, tungsten, or any combinations thereof. In one embodiment, oneor more of the guidewires may be made of a polymer, with an electricallyconductive core for transmitting electrical energy to the respectiveelectrodes. The cross-sectional area of the longitudinal members and/orthe delivery element may be configured to progressively increase fromthe distal end towards the proximal end. The tapered configuration maybe advantageous in that the narrow distal end may be configured toeffectively traverse through the tortuous tissue region such as vascularmatrix and to penetrate the occlusion and/or the subintimal space,whereas the larger proximal end is configured to allow a user tomanipulate the longitudinal members during the operation. Alternativelyand optionally, a cross-sectional area of the longitudinal members maybe configured to be substantially unchanged throughout the lengths ofthe longitudinal members.

It is noted that the flexibility of the longitudinal members may varyover their respective lengths. In one embodiment, the distal ends may besubstantially flexible, and the flexibility progressively decreasestowards the proximal ends.

Optionally, the longitudinal members of the present embodiments maycomprise at least a layer of structural polymer over the core wire.Additionally and optionally, an outer surface of the longitudinalmembers may be coated with hydrophilic coating for ease of navigationthrough tortuous passageways.

In addition to the retrograde/antegrade approach as described above, itis contemplated that the present embodiments may be configured todeliver a composition to a treatment region such as an occluded vesselby penetrating the distal cap of the occlusion without approaching thedistal cap from the retrograde direction through an intercoronarychannel. Thereafter, one or more compositions may be delivered and RFenergy may be delivered in a bipolar arrangement between twolongitudinal members to generate an energy field as described above. Asdescribed in co-pending PCT application PCT/US2011/031018 by the sameinventors, which is incorporated herein in its entirety, the distal endof one or more longitudinal members may be configured to be capable ofbeing redirected. Similarly, present embodiments contemplate that atleast a portion of the composition delivery element as disposed on thelongitudinal member may likewise be redirected.

The present embodiments further contemplate delivering one or morecompositions in conjunction to the antegrade and retrograde tracking(CART) techniques as disclosed in the U.S. Pat. No. 7,918,859. In suchembodiments, a composition may be delivered during the various stages ofthe antegrade and retrograde procedures without using an energymodality. For example, a composition such as a biocompatible compressedgas may be delivered to the occluded vessel using the delivery elementto create, enlarge, or expand a space in the occlusion to facilitatefurther penetration of the occlusion by the longitudinal member orcomposition delivery. Furthermore, a therapeutic agent such ascollagenase may be delivered to the occluded vessel to soften theocclusion.

While the above embodiments refer to the use of RF energy for thepurpose of generating an energy field and ablation, it should be notedthat other energy modalities may be used as well. For example, in oneembodiment, one or more longitudinal members comprise one or moreultrasound transducers, instead of or in addition to RF electrodes. Theultrasound transducers provide ultrasound energy for ablating anocclusion. In one embodiment, the antegrade and/or the retrogradelongitudinal members may comprise ultrasound transducers and ablate theocclusion from an antegrade as well as a retrograde direction. Otherenergy modalities could include microwave and laser.

It should be noted that the combined antegrade and retrograde energydelivery techniques described above could also be used as an adjuncttechnique to crossing CTOs in combination with using conventionalmethods. The technique could be used to sufficiently soften or weakenthe occlusion, thereby allowing a guidewire or catheter to cross theocclusion.

Additionally, it is noted that the present embodiments are applicable tovarious treatment regions, and are not limited to coronary occlusions.For example, present embodiments may be used deliver therapeutic ordiagnostic agents to any site within the vascular system. For example,in oncology, one or both of longitudinal members may used to injecttherapeutic agents such as SFU, doxorubicin, adriamycin, etc. at thesite of a tumor. As another example, in interventional neuroradiology,one or both of the longitudinal members may be used to diagnose or treataneurysms or fistulas by delivering therapeutic or diagnostic agentsincluding coils, polymers, gels, etc.

It is contemplated that the present embodiments may be used to deliverother therapeutic agents or other biologically active substancesincluding but not limited to: amino acids, anabolics, analgesics andantagonists, anesthetics, anthelmintics, anti-adrenergic agents,anti-asthmatics, anti-atherosclerotics, antibacterials,anticholesterolics, anti-coagulants, antidepressants, antidotes,anti-emetics, anti-epileptic drugs, ant-fibrinolytics, anti-inflammatoryagents, antihypertensives, antimetabolites, antimigraine agents,antimycotics, antinauseants, antineoplastics, anti-obesity agents,anti-Parkinson agents, antiprotozoals, antipsychotics, antirheumatics,antiseptics, antivertigo agents, antivirals, bacterial vaccines,bioflavonoids, calcium channel blockers, capillary stabilizing agents,coagulants, corticosteroids, detoxifying agents for cytostatictreatment, contrast agents (like contrast media, radioisotopes, andother diagnostic agents), electrolytes, enzymes, enzyme inhibitors,gangliosides and ganglioside derivatives, hemostatics, hormones, hormoneantagonists, hypnotics, immunomodulators, immunostimulants,immunosuppressants, minerals, muscle relaxants, neuromodulators,neurotransmitters and nootropics, osmotic diuretics, parasympatholytics,para-sympathomimetics, peptides, proteins, respiratory stimulants,smooth muscle relaxants, sympatholytics, sympathomimetics, vasodilators,vasoprotectives, vectors for gentherapy, viral vaccines, viruses,vitamins, and the like.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

What is claimed is:
 1. A composition delivery system, comprising: afirst longitudinal member coupled to an energy source and comprising afirst conductive electrode disposed on a distal end of the firstlongitudinal member; and a second longitudinal member coupled to theenergy source comprising a second conductive electrode disposed on adistal end of the second longitudinal member, wherein at least one ofthe first longitudinal member or the second longitudinal member furthercomprises a delivery element disposed within an interior lumen of the atleast one of the first longitudinal member or the second longitudinalmember, the delivery element comprising a delivery shaft disposedbetween a distal delivery port and a proximal supply port to deliver acomposition from the proximal supply port, through the delivery shaft,to the distal delivery port and to a body region, wherein the firstconductive electrode and the second conductive electrode are disposed onthe first and second longitudinal members, respectively, such that whenpositioned in the body region and energized by the energy source thefirst conductive electrode and the second conductive electrode generatean energy field such that migration of the composition delivered throughthe distal delivery port to the body region is in a direction that isinfluenced by the generated energy field.
 2. The device of claim 1,wherein the second longitudinal member is spaced apart and entirelyseparate in a non-overlapping arrangement from the first longitudinalmember, such that the first longitudinal member is configured toapproach the body region in an antegrade fashion and the secondlongitudinal member is configured to approach the body region in aretrograde fashion.
 3. The device of claim 1, wherein the energy sourceis a radiofrequency energy source.
 4. The device of claim 1, wherein thefirst conductive electrode is an active electrode and the secondconductive electrode is a passive electrode.
 5. The device of claim 1,wherein the first conductive electrode and the second conductiveelectrode are configured to generate the energy field such that themigration of the composition in the body region is from the firstconductive electrode to the second conductive electrode.
 6. The deviceof claim 1, wherein the composition is delivered in a bi-directionalfashion between the first and second conductive electrodes.
 7. Thedevice of claim 1, further comprising at least one composition reservoirin fluid communication with the proximal supply port and configured tohold the composition.
 8. The device of claim 7, wherein the compositionreservoir is connected to the delivery element through one or morelumens disposed within the first or the second longitudinal members. 9.The device of claim 1, wherein the longitudinal members are guidewires,catheters, micro-catheters, or dilating catheters.
 10. The device ofclaim 1, wherein the energy source is configured to generate an electricfield, a magnetic field, or ultrasonic field.
 11. The device of claim 1,further comprising the composition, wherein the composition comprises aconductive fluid to form an energy path between the first conductiveelectrode and the second conductive electrode.
 12. The device of claim11, wherein the energy path is configured to facilitate energytransmission between the first and the second conductive electrodes. 13.The device of claim 11, wherein the conductive fluid is configured toablate a portion of the body region.
 14. The device of claim 11, whereinthe conductive fluid is saline.
 15. The device of claim 1, wherein thebody region is a vessel comprising an occlusion.
 16. The device of claim1, further comprising the composition wherein the composition comprisescollagenase.
 17. The device of claim 1, wherein the composition is abiocompatible gas.
 18. A recanalization system, comprising: a firstlongitudinal member capable of being advanced in an antegrade fashionthrough a proximal end of an occlusion in an occluded vessel; and asecond longitudinal member capable of being advanced in an retrogradefashion through a distal end of the occlusion, wherein at least one ofthe first longitudinal member or the second longitudinal member furthercomprises a delivery element disposed within an interior lumen of the atleast one of the first longitudinal member or the second longitudinalmember, the delivery element comprising a delivery shaft disposedbetween a distal delivery port and a proximal supply port to deliver acomposition from the proximal supply port, through the delivery shaft,to the distal delivery port and to the occluded vessel to treat theoccluded vessel.
 19. The device of claim 18, wherein the firstlongitudinal member and the second longitudinal member are configured tocooperate to form a channel inside the occluded vessel.
 20. The deviceof claim 18 further comprising a composition reservoir connected to thedelivery element through one or more lumens disposed within the first orthe second longitudinal members.
 21. The device of claim 18, wherein thelongitudinal members are guidewires, catheters, micro-catheters, ordilating catheters.
 22. The device of claim 18, wherein the firstlongitudinal member further comprises a first conductive electrodedisposed on a distal end of the first longitudinal member and the secondlongitudinal member comprises a second conductive electrode disposed ona distal end of the second longitudinal member, wherein the first andthe second longitudinal members are connected to an energy source suchthat the first conductive electrode and the second conductive electrodeare configured to generate an energy field.
 23. The device of claim 22,wherein the first conductive electrode and the second conductiveelectrode are disposed on the first and second longitudinal members,respectively, such that when positioned in the body region and energizedby the energy source the first conductive electrode and the secondconductive electrode generate the energy field such that migration ofthe composition delivered through the distal delivery port to the bodyregion is in a direction that is influenced by the generated energyfield.
 24. The device of claim 18 further comprising the composition,wherein the composition is configured to soften the occlusion.
 25. Thedevice of claim 24, wherein the composition comprises collagenase. 26.The device of claim 18, wherein the second longitudinal member is spacedapart and entirely separate in a non-overlapping arrangement from thefirst longitudinal member.